1. Technical Field of the Invention
The present invention relates to novel dermatological/pharmaceutical compositions comprising at least one lanthanide, manganese, tin, zinc, yttrium, cobalt, barium or strontium salt as a substance P antagonist, for the treatment of and/or alleviation of pain associated with at least one of the following skin disorders, including those of the scalp and mucous membranes: zona, poszoster, scald or burns, demodicidosis, skin ulcer, fibrosis and/or controlling hypertrophic cicatrization and/or treating acne rosacea.
2. Description of the Prior Art
Polypeptides belonging to the tachykinin family exist in mammals which induce rapid contractions of the smooth muscle fibers. Exemplary compounds of this family include .beta.-neurokinin, .alpha.-neurokinin and substance P.
Substance P is a polypeptide chemical species (undecapeptide), produced and released by a nerve ending. The location of substance P is specific to the neurons, both in the central nervous system and in the organs at the periphery. Thus, very many organs or tissues receive afferences of substance P neurons; these are especially the salivary glands, stomach, pancreas, intestine (in the latter, the distribution of substance B is superposed on the intrinsic Meissner and Auerbach nervous plexus), cardiovascular system, thyroid gland, skin, iris and ciliary bodies, bladder and, obviously, the central and peripheral nervous systems.
By virtue of the ubiquitous distribution of substance P, very many disorders are associated with an excessive synthesis and/or release of substance P.
Substance P is involved, in particular, in the transmission of pain (dental, cutaneous, tympanic) and in diseases of the central nervous system (for example anxiety, psychoses, neuropathies, neurodegenerative disorders of the Alzheimer senile dementia type, dementia in Aids patients, Parkinson's disease, Down's syndrome, Korsakoff's syndrome, multiple scleroses, schizophrenia, psychotic diseases), in respiratory diseases (such as, for example, bronchial pneumonia, cough, emphysema, bronchiolitis) and inflammatory diseases (such as, for example, rheumatoid arthritis), in allergic syndromes (for example asthma, allergic rhinitis, allergic pharyngitis, urticaria, eczematous dermatitis), in gastrointestinal diseases (such as, for example, ulcers, colitis, Crohn's disease, gastritis, gastroenteritis, intestinal spasticities), in skin disorders (such as, for example, psoriasis, prurigenous diseases, herpes, photodermatosis, atopic dermatitis, contact dermatitis, lichens, prurigos, pruritus, rosacea, ulcers, zona, demodicidoses, acne rosacea, sensitive skins, dartres, solar and emotional erythemas, insect burns), in fibroses and other collagen maturation disorders (such as, for example, scleroderma), in cardiovascular diseases, vasospastic disorders (such as, for example, migraine, Raynaud's disease), in immunological disorders, in disorders of the urinary or genital tract (such as, for example, incontinence, cystitis), in rheumatic diseases, in certain dermatological diseases (such as eczema) and in ophthalmological conditions (such as, for example, conjunctivitis, uveitis, ocular pruritus, blepharitis, irritations and ocular pain).
The administration of a substance P antagonist is one of the therapeutic alternatives which are effective in all of the conditions and afflictions indicated above.
By "substance P antagonist" is intended any compound or species capable of partially, or even completely inhibiting the biological effect of substance P. In particular, for a substance to be recognized as a substance P antagonist, it must induce a coherent pharmacological response (including or otherwise its binding to the substance P receptor), in particular in one of the following tests:
(a) the antagonist substance must reduce the extravasation of the plasma across the vascular wall induced by capsaicin or by an antidromic nerve stimulation, or, alternatively; PA1 (b) the antagonist substance must cause inhibition of the contraction of the smooth muscles induced by the administration of substance P. PA1 Exemplary active agents include: PA1 (1) skin pigmentation and/or proliferation and/or differentiation modulating agents, such as retinoic acid and isomers thereof, retinol and esters thereof, vitamin D and derivatives thereof, estrogens such as estradiol, kojic acid or hydroquinone; PA1 (2) antibacterial agents such as clindamycin phosphate, erythromycin or antibiotics of the tetracycline class; PA1 (3) antiparasitic agents, in particular metronidazole, crotamiton or pyrethrinoids; PA1 (4) antifungal agents, in particular the compounds belonging to the imidazole class such as econozale, ketoconazole or miconazole or salts thereof, polyene compounds such as amphotericin B, compounds of the allylamine family, such as terbinafine, or alternatively octopirox; PA1 (5) antiviral agents such as acyclovir; PA1 (6) steroidal anti-inflammatory agents such as hydrocortisone, betamethasone valerate or clobetasol propionate, or nonsteroidal anti-inflammatory agents such as ibuprofen and salts thereof, diclofenac and salts thereof, acetylsalicylic acid, acetaminophen or glycyrrhetinic acid; PA1 (7) anaesthetic agents such as lidocaine hydrochloride and derivatives thereof; PA1 (8) antipruritic agents such as thenaldine, trimeprazine or cyproheptadine; PA1 (9) keratolytic agents such as alpha- and beta-hydroxycarboxylic or -ketocarboxylic acids, their salts, amides or esters and, more particularly, hydroxy acids such as glycolic acid, lactic acid, salicylic acid, citric acid and, in general, fruit acids, and n-octanoyl-5-salicylic acid; PA1 (10) anti-free radical agents such as alpha-tocopherol or esters thereof, superoxide dismutases, certain metal chelators or ascorbic acid and esters thereof; PA1 (11) antiseborrhoeic agents such as progesterone; PA1 (12) antidandruff agents such as octopirox or zinc pyrithione; PA1 (13) antiacne agents such as retinoic acid or benzoyl peroxide; PA1 (14) antiseptics; PA1 (15) antimetabolites.
To date, substance P antagonists have been administered to treat the disorders indicated above.
Nonetheless, it was hitherto unknown that a lanthanide, zinc, yttrium, tin, cobalt, barium or strontium salt exhibited a substance P antagonizing activity as defined above and thus could be useful for treating the pain associated with the various skin conditions and/or disorders indicated above.
In addition, a formulation containing cresols and strontium chloride for increasing the antibacterial and antimicrobial properties of such cresols is described in FR-M-5394. However, it is neither described nor suggested that the strontium chloride can, by itself alone, decrease or indeed eliminate symptoms such as irritation, pain, itching or smarting caused by any disease nor decrease or indeed eliminate the same symptoms elicited by an irritant product.